This invention relates to methods for identifying patients with increased risk of experiencing an adverse cardiovascular event. The invention also relates to the determination of platelet hyperactivity in a patient undergoing aspirin anti-platelet therapy as an indication of an increased risk of suffering a cardiovascular event.
The term “cardiovascular disease” refers to a class of diseases that involve the heart and/or blood vessels (arteries and veins), i.e., any disease that affects the cardiovascular system. Over fifty million Americans have cardiovascular problems, and most other Western countries face high and increasing rates of cardiovascular disease. It is the number one cause of death and disability in the United States and most European countries.
The role of platelets in mammalian physiology is extraordinarily diverse, but their primary role is in promoting hemostasis. When exposed to a damaged blood vessel, platelets will adhere to an exposed sub-endothelial matrix. Following the initial adhesion, various factors released at the site of injury such as thrombin, ADP and collagen activate the platelets. Once platelets are activated, a conformational change occurs in the platelet glycoprotein GPIIb/IIIa receptor allowing it to bind fibrinogen and/or von Willebrand factor. It is this binding of the multivalent fibrinogen and/or von Willebrand factor molecules by GPIIb/IIIa receptors on adjacent platelets that results in the recruitment of additional platelets to the site of injury and their aggregation to form a hemostatic plug or thrombus.
Questions of interest include whether to administer drugs that will block, or promote, clot formation, or whether to detect deficiencies in platelet function prior to surgical procedures. Platelets are known to play an active role in the development of cardiovascular disease (CVD). Consequently, therapeutic strategies to inhibit platelet function are extremely important.
Millions of people are taking aspirin, the oldest and most widely used platelet inhibiting agent, as therapy to reduce the risk of heart attacks and other cardiovascular events. These include persons that have previously suffered a cardiovascular event as well as those with elevated cholesterol, a family history of heart disease, or other risk factors for cardiovascular disease. Among those with risk factors, many persons that have had a heart attack or other cardiovascular event are prescribed some anti-platelet agent, usually aspirin. Aspirin (acetyl salicylic acid) effectively reduces the risk of secondary thrombotic events in individuals who have experienced angina, myocardial infarct, peripheral artery disease, or cerebrovascular ischemia. Aspirin also may reduce the risk of initial thrombotic events in healthy individuals and many healthy people without a recognized elevated risk of cardiovascular disease also take aspirin as a precaution. For this reason, many individuals, through physician prescriptions or self-medication, take aspirin on a regular basis for the primary or secondary prevention of thrombotic disease.
However, it is known that aspirin reduces ischemic vascular events by only about 22%. Poor responsiveness to aspirin, as measured by various laboratory tests, is associated with vascular ischemic disorders including myocardial infarction, coronary artery disease and stroke.
It would be desirable, therefore, to be able to determine the likelihood of a patient undergoing aspirin therapy to experience an adverse cardiovascular event. It would be desirable to identify patients with increased risk of a major adverse cardiovascular event even while undergoing aspirin therapy. The ability to identify high-risk individuals would allow physicians to focus preventive measures on those individuals, who may gain the greatest benefit, and would provide strong incentives for those at risk to comply with such approaches.